Toxic effects of hexachlorobenzene after daily administration to beagle dogs for one year

Gralla, Edward J.; Fleischman, Robert W.; Luthra, Yugal K.; Hagopian, Miasnig; Baker, John; Esber, Henry J.; Marcus, William L.

doi:10.1016/0041-008x(77)90093-x

Cited by 34 publications

(10 citation statements)

References 29 publications

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“…Hyperplasia of the gastric lymphoid tissue was also frequently observed in dogs of all dose groups. Moreover, in the high-dose group, 33% of the dogs displayed arteritis-periarteritis of small arteries and arterioles affecting multiple organ sites (81).…”

Section: Accidental Human Poisoning In Turkeymentioning

confidence: 99%

The role of the immune system in hexachlorobenzene-induced toxicity.

Michielsen

Loveren

Vos

1999

Environ Health Perspect

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Hexachlorobenzene (HCB) is a persistent environmental pollutant. The toxicity of HCB has been extensively studied after an accidental human poisoning in Turkey and more recently it has been shown that HCB has immunotoxic properties in laboratory animals and probably also in man. Oral exposure of rats to HCB showed stimulatory effects on spleen and lymph node weights and histology, increased serum IgM levels, and an enhancement of several parameters of immune function. Moreover, more recent studies indicate that HCB-induced effects in the rat may be related to autoimmunity. In Wistar rats exposed to HCB, IgM antibodies against several autoantigens were elevated; in the Lewis rat, HCB differently modulated two experimental models of autoimmune disease. Oral exposure of rats to HCB induces skin and lung pathology in the rat. Recently several studies have been conducted to investigate whether these skin and lung lesions can be related to HCB-induced immunomodulation, and these studies will be discussed in this review. HCB-induced skin and lung lesions probably have a different etiology; pronounced strain differences and correlation of skin lesions with immune parameters suggest a specific involvement of the immune system in HCB-induced skin lesions. The induction of lung lesions by HCB was thymus independent. Thymus-dependent T cells were not likely to be required for the induction of skin lesions, although T cells enhanced the rate of induction and the progression of the skin lesions. No deposition of autoantibodies was observed in nonlesional or lesional skin of HCB-treated rats. Therefore, we concluded that it is unlikely that the mechanism by which most allergic or autoimmunogenic chemicals work, i.e., by binding to macromolecules of the body and subsequent T-and B-cell activation, is involved in the HCB-induced immunopathology in the rat. Such a thymus-independent immunopathology is remarkable, as HCB strongly modulates T-cell-mediated immune parameters. This points at a very complex mechanism and possible involvement of multiple factors in the immunopathology of HCB.

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Section: Accidental Human Poisoning In Turkeymentioning

confidence: 99%

The role of the immune system in hexachlorobenzene-induced toxicity.

Michielsen

Loveren

Vos

1999

Environ Health Perspect

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“…Proliferation of lymph node, high endothelial venules following HCB exposure noted by Kitchin et al (35), as well as Vos et al (36), in rats at prenatal and postnatal HCB doses of 50 mg/kg/day may alter Tand B-lymphocyte trafficking and explain these differential effects. Hyperplasia of gut-associated lymphoid tissues was also noted in dogs administered as little as 1 mg/kg/day (37), providing further histological evidence for an effect of HCB on the immune system.…”

Section: Hexachiorobenzenementioning

confidence: 78%

Pesticide-Induced Immunotoxicity: Are Great Lakes Residents at Risk?

Thomas¹

1995

Environmental Health Perspectives

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Several organophosphate and organochlorine compounds, including pesticides commonly found in the Great Lakes basin, have the potential to induce immunotoxicity. Because of biomagnification and accumulation in the food chain, Great Lakes residents may inadvertently be exposed to these compounds and thus face increased risk of immune dysfunction. In spite of the laboratory animal data and evidence from occupational exposures that suggest immunotoxicity, there is no definitive evidence as yet that environmental exposure to these xenobiotics poses a significant threat to the human immune system that is sufficient to predispose residents of the Great Lakes basin to increased disease. However, uncertainties with regard to exposure levels, predictability of tests, suitability of the animal models, and immune reserve cannot be ruled out when making risk assessment decisions such as this. -Environ Health Perspect 1 03(Suppl 9): 55-61 (1995)

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“…Liver changes as described in our study and/or changes in biochemical parameters in blood and feces are not restricted to dogs (Gralla et al, 1977). In other laboratory species such as mice, rats and genetically engineered (ferrochelatase deficient) mice, such changes have been described as well after drug-treatment (Zaki et al, 1973;Matilla and Molland, 1974;Cantoni et al, 1983;Tutois et al, 1991;Frater et al, 1993;Smith et al, 1997).…”

Section: Discussionmentioning

confidence: 90%

“…Domestic animals mainly develop congenital and hereditary porphyria (With, 1980) whereas in laboratory animals (rats and mice) drug-induced porphyria have been described in literature (Matilla and Molland, 1974;Gralla et al, 1977;Cantoni et al, 1983;Frater et al, 1993;Smith, 1997). For dogs, information about experimentally induced porphyria is scarce and not of recent date (Stokvis, 1895;Zaki et al, 1973;Stejskal et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

Drug-Induced Protoporphyria in Beagle Dogs

Putten¹,

Esch²,

Kamerman³

et al. 2005

Toxicol Pathol

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As part of regulatory safety testing program, a 13-week oral toxicity study with a new antipsychotic drug candidate was performed in beagle dogs. During this study, dark red/brown feces were recorded in treated dogs and increases in liver parameters (alanine aminotransferase, alkaline phosphatase, bilirubin) were measured biochemically. At the end of the study, livers of high-dose (50 mg/kg) animals were (mottled) dark brown, sometimes with pale foci. Histopathological examination of these livers showed dark globular pigment deposits in the hepatocellular cytoplasm and within the bile canaliculi. Varying numbers of inflammatory cell infiltrates were additionally present in association with the deposits. These pigment deposits showed birefringency with characteristic "Maltese Cross"-like structures under polarized light. Electronmicroscopy revealed the typical, so-called "sunburst" pattern with radiating double-lined crystalline structures. These morphologic characteristics strongly indicated at the presence of porphyrins, which was definitely confirmed biochemically. Published reports of drug-induced hepatic porphyria in dogs are rare. The possible underlying mechanism in the dog and man is discussed.

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Toxic effects of hexachlorobenzene after daily administration to beagle dogs for one year

Cited by 34 publications

References 29 publications

The role of the immune system in hexachlorobenzene-induced toxicity.

The role of the immune system in hexachlorobenzene-induced toxicity.

Pesticide-Induced Immunotoxicity: Are Great Lakes Residents at Risk?

Drug-Induced Protoporphyria in Beagle Dogs

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